Scalable Bioelectronic Production of Extracellular Vesicles for Cardiac Tissue Regeneration
- PMID: 41179998
- PMCID: PMC12574593
- DOI: 10.1016/j.device.2025.100968
Scalable Bioelectronic Production of Extracellular Vesicles for Cardiac Tissue Regeneration
Abstract
EV-based therapies are hindered by low production efficiency and poor scalability. Conventional methods to enhance EV yield-such as hypoxia or chemical stimulation-often compromise vesicle quality and cell health. This study introduces a bioelectronic platform featuring a planar interdigitated electrode array that enables simultaneous low-voltage (±1 V), low-frequency (2 Hz) biphasic stimulation and real-time super-resolution imaging of EV biogenesis via TIRF microscopy. This bioelectrical stimulation on primary cardiac cells significantly increases EV secretion without affecting cell viability. The resulting electrically-induced EVs (e-EVs) exhibit enhanced microRNA cargo-loading capacity, preserved tissue tropism, and functional therapeutic potential. In a murine model of acute myocardial infarction, miRNA-loaded e-EVs improved cardiac function and reduced fibrosis. These results highlight the potential of bioelectronic modulation as a scalable, non- destructive strategy for improving EV yield and functional performance in translational regenerative medicine.
Conflict of interest statement
Declaration of Interests B.T., L.M., P.L., and W.L, are inventors on a U.S. patent application (US20240101997A1) filed by the University of Chicago that covers device and method for electrically stimulated production of extracellular vesicles. The patent relates to aspects of the bioelectronic platform, stimulation protocols, and therapeutic applications described in this study. All other authors declare no competing interests.
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